Inhibition of monocyte complement receptor enhancement by low molecular weight material from human lung cancers

We have studied the effect of dialysates from lung cancer homogenates to alter both the expression of complement (C3b) receptors per se and also to inhibit leucoattractant-induced enhancement of complement rosettes on monocytes from healthy individuals. Enhancement and enhancement-inhibition by tumour extracts were compared with material derived from normal lung excised from distance from the tumour. There was no significant difference between tumour homogenate (TH) and normal lung homogenate (NLH) in terms of enhancement of complement rosettes per se. In contrast, TH produced a dose- and time-dependent inhibition of leucoattractant-induced enhancement of C3b rosettes which was significantly different from that obtained with NLH. This enhancement-inhibition was observed with four undifferentiated, four squamous and three adenocarcinomas of lung. The degree of enhancement-inhibition was not related to the type of tumour or varying accompanying histological features such as necrosis and the degree of infiltration with inflammatory cells. Following gel filtration on Sephadex G-50 each type of cancer gave a major peak of inhibitory activity which eluted with molecules having an apparent molecular size of approximately 3,000 daltons. A second larger peak (8,000-10,000 daltons) was also detected with extracts from the undifferentiated and adenocarcinomas. These results support previous findings, mainly from experimental animals, indicating that 'anti-macrophage/monocyte principles' are elaborated from certain tumour types

A development of logistics management models for the Space Transportation System

A new analytic queueing approach was described which relates stockage levels, repair level decisions, and the project network schedule of prelaunch operations directly to the probability distribution of the space transportation system launch delay. Finite source population and limited repair capability were additional factors included in this logistics management model developed specifically for STS maintenance requirements. Data presently available to support logistics decisions were based on a comparability study of heavy aircraft components. A two-phase program is recommended by which NASA would implement an integrated data collection system, assemble logistics data from previous STS flights, revise extant logistics planning and resource requirement parameters using Bayes-Lin techniques, and adjust for uncertainty surrounding logistics systems performance parameters. The implementation of these recommendations can be expected to deliver more cost-effective logistics support

Meteoritic Material Recovered from the 07 March 2018 Meteorite Fall into the Olympic Coast National Marine Sanctuary

On 07 March 2018 at 20:05 local time (08 March 03:05 UTC), a dramatic meteor occurred over Olympic Coast National Marine Sanctuary (OCNMS) off of the Washington state coast (OCNMS fall, henceforth). Data to include seismometry (from both on-shore and submarine seismometers), weather radar imagery (Figure 1), and a moored weather buoy, were used to accurately identify the fall site. The site was visited by the exploration vessel E/V Nautilus (Ocean Exploration Trust) on 01 July 2018 [1] and by the research vessel R/V Falkor (Schmidt Ocean Institute) from 03-06 June 2019. Remotely operated vehicles (ROVs) from both vessels were used to search for meteorites and sample seafloor sediments. These expeditions performed the first attempts to recover meteorites from a specific observed fall in the open ocean. Analysis of weather radar data indicates that this fall was unusually massive and featured meteorites of unusually high mechanical toughness, such that large meteorites were disproportionately produced compared to other meteorite falls (Figure 2)[2-4]. We report the recovery of many (>100) micrometeorite-sized melt spherules and other fragments, and one small (~1mm3 ) unmelted meteorite fragment identified to date. Approximately 80% of the fragments were recovered from a single sample, collected from a round pit in the seafloor sediment. Melt spherules are almost exclusively type I iron-rich spherules with little discernible oxidation. Analyses are currently underway to attempt to answer the primary science question by identifying the parent meteorite type. Also, differences in the number and nature of samples collected by Nautilus and Falkor reveal a distinct loss rate to oxidation over the 15 months following the fall that is useful to inform future recovery efforts

NASA's Asteroid Redirect Mission: A Robotic Boulder Capture Option for Science, Human Exploration, Resource Utilization, and Planetary Defense

NASA is examining two options for the Asteroid Redirect Mission (ARM), which will return asteroid material to a Lunar Distant Retrograde Orbit (LDRO) using a robotic solar electric propulsion spacecraft, called the Asteroid Redirect Vehicle (ARV). Once the ARV places the asteroid material into the LDRO, a piloted mission will rendezvous and dock with the ARV. After docking, astronauts will conduct two extravehicular activities (EVAs) to inspect and sample the asteroid material before returning to Earth. One option involves capturing an entire small (~4 - 10 m diameter) near-Earth asteroid (NEA) inside a large inflatable bag. However, NASA is also examining another option that entails retrieving a boulder (~1 - 5 m) via robotic manipulators from the surface of a larger (~100+ m) pre-characterized NEA. The Robotic Boulder Capture (RBC) option can leverage robotic mission data to help ensure success by targeting previously (or soon to be) well- characterized NEAs. For example, the data from the Japan Aerospace Exploration Agency's (JAXA) Hayabusa mission has been utilized to develop detailed mission designs that assess options and risks associated with proximity and surface operations. Hayabusa's target NEA, Itokawa, has been identified as a valid target and is known to possess hundreds of appropriately sized boulders on its surface. Further robotic characterization of additional NEAs (e.g., Bennu and 1999 JU3) by NASA's OSIRIS REx and JAXA's Hayabusa 2 missions is planned to begin in 2018. This ARM option reduces mission risk and provides increased benefits for science, human exploration, resource utilization, and planetary defense. Science: The RBC option is an extremely large sample-return mission with the prospect of bringing back many tons of well-characterized asteroid material to the Earth-Moon system. The candidate boulder from the target NEA can be selected based on inputs from the world-wide science community, ensuring that the most scientifically interesting boulder be returned for subsequent sampling. In addition, the material surrounding the boulder can be collected from the surface, thus providing geological contextual information and additional samples of NEA regolith. The robotic manipulators used for capturing the boulder will ensure some of the surface remains undisturbed and that the boulder will retain its structural integrity, which will preserve the context of any samples collected by the astronauts and ensure a high level of science return. Human Exploration: Due to the coherent nature of the boulder that will be collected, entire encapsulation of the asteroid material is not required. This facilitates exploration and sample collection of the boulder by astronauts in a variety of ways. The total time for EVA during the crew portion of the mission is very limited. Current estimates are that each of the two EVAs will only last four hours. The RBC option will allow crew members to have good situational awareness of the work site and quickly identify sample sites of interest. In addition, the samples to be collected can be readily accessed without having to deal with removal of an encapsulation system, which adds extra complexity and risk for the astronauts during EVA. Resource Utilization: One of the most crucial aspects for resource utilization is the identification and collection of appropriate materials (e.g., volatiles, organics, metals, etc.) that contain components of interest. Prior characterization of NEAs is required in order to increase the likelihood that appropriate materials will be returned. Ground-based observations of small (<10 m) NEAs are challenging, but characterization efforts of larger targets have demonstrated that NEAs with volatiles and organics have been identified. Two potential targets for the RBC option (Bennu and 1999 JU3) have been previously identified as potentially rich in resources, and both are already targets of currently planned robotic missions that will characterize their physical properties in great detail. Planetary Defense: The RBC option involves interaction with a well- characterized potentially hazardoussized NEA that would enable NASA to conduct one or more planetary defense demonstrations. The primary method would use the collected boulder to augment the mass of the ARV and perform an Enhanced Gravity Tractor (EGT) demonstration on the NEA. Additionally, other approaches could be demonstrated during the mission, such as Ion Beam Deflection (IBD) and/or observation of a Kinetic Impactor (KI). The relative effectiveness of a slow push-pull method such as the EGT or IBD could be directly compared and contrasted with the results of the more energetic KI method on the target NEA. Conclusions: This boulder option for NASA's ARM can leverage knowledge of previously characterized NEAs from prior robotic missions, which provides more certainty of the target NEA's physical characteristics and reduces mission risk. This increases the return on investment for NASA's future activities with respect to human exploration, resource utilization, and planetary defense

NASA's Asteroid Redirect Mission: The Boulder Capture Option

NASA is examining two options for the Asteroid Redirect Mission (ARM), which will return asteroid material to a Lunar Distant Retrograde Orbit (LDRO) using a robotic solar-electric-propulsion spacecraft, called the Asteroid Redirect Vehicle (ARV). Once the ARV places the asteroid material into the LDRO, a piloted mission will rendezvous and dock with the ARV. After docking, astronauts will conduct two extravehicular activities (EVAs) to inspect and sample the asteroid material before returning to Earth. One option involves capturing an entire small (approximately 4-10 m diameter) near-Earth asteroid (NEA) inside a large inflatable bag. However, NASA is examining another option that entails retrieving a boulder (approximately 1-5 m) via robotic manipulators from the surface of a larger (approximately 100+ m) pre-characterized NEA. This option can leverage robotic mission data to help ensure success by targeting previously (or soon to be) well-characterized NEAs. For example, the data from the Hayabusa mission has been utilized to develop detailed mission designs that assess options and risks associated with proximity and surface operations. Hayabusa's target NEA, Itokawa, has been identified as a valid target and is known to possess hundreds of appropriately sized boulders on its surface. Further robotic characterization of additional NEAs (e.g., Bennu and 1999 JU3) by NASA's OSIRIS REx and JAXA's Hayabusa 2 missions is planned to begin in 2018. The boulder option is an extremely large samplereturn mission with the prospect of bringing back many tons of wellcharacterized asteroid material to the EarthMoon system. The candidate boulder from the target NEA can be selected based on inputs from the worldwide science community, ensuring that the most scientifically interesting boulder be returned for subsequent sampling. This boulder option for NASA's ARM can leverage knowledge of previously characterized NEAs from prior robotic missions, which provides more certainty of the target NEA's physical characteristics and reduces mission risk. This increases the return on investment for NASA's future activities with respect to science, human exploration, resource utilization, and planetary defens

Successful use of axonal transport for drug delivery by synthetic molecular vehicles

We report the use of axonal transport to achieve intraneural drug delivery. We constructed a novel tripartite complex of an axonal transport facilitator conjugated to a linker molecule bearing up to a hundred reversibly attached drug molecules. The complex efficiently enters nerve terminals after intramuscular or intradermal administration and travels within axonal processes to neuron cell bodies. The tripartite agent provided 100-fold amplification of saturable neural uptake events, delivering multiple drug molecules per complex. _In vivo_, analgesic drug delivery to systemic and to non-targeted neural tissues was greatly reduced compared to existing routes of administration, thus exemplifying the possibility of specific nerve root targeting and effectively increasing the potency of the candidate drug gabapentin 300-fold relative to oral administration

Microstructured optical fiber-based biosensors: reversible and nanoliter-scale measurement of zinc ions

Published: May 6, 2016Sensing platforms that allow rapid and efficient detection of metal ions would have applications in disease diagnosis and study, as well as environmental sensing. Here, we report the first microstructured optical fiber-based biosensor for the reversible and nanoliter-scale measurement of metal ions. Specifically, a photoswitchable spiropyran Zn(2+) sensor is incorporated within the microenvironment of a liposome attached to microstructured optical fibers (exposed-core and suspended-core microstructured optical fibers). Both fiber-based platforms retains high selectivity of ion binding associated with a small molecule sensor, while also allowing nanoliter volume sampling and on/off switching. We have demonstrated that multiple measurements can be made on a single sample without the need to change the sensor. The ability of the new sensing platform to sense Zn(2+) in pleural lavage and nasopharynx of mice was compared to that of established ion sensing methodologies such as inductively coupled plasma mass spectrometry (ICP-MS) and a commercially available fluorophore (Fluozin-3), where the optical-fiber-based sensor provides a significant advantage in that it allows the use of nanoliter (nL) sampling when compared to ICP-MS (mL) and FluoZin-3 (μL). This work paves the way to a generic approach for developing surface-based ion sensors using a range of sensor molecules, which can be attached to a surface without the need for its chemical modification and presents an opportunity for the development of new and highly specific ion sensors for real time sensing applications.Sabrina Heng, Christopher A. McDevitt, Roman Kostecki, Jacqueline R. Morey, Bart A. Eijkelkamp, Heike Ebendorff-Heidepriem, Tanya M. Monro, and Andrew D. Abel

Correlation length of X-ray brightest Abell clusters

We compute the cluster auto-correlation function $\xi_{cc}(r)$ of an X-ray flux limited sample of Abell clusters (XBACs, \cite{ebe}). For the total XBACs sample we find a power-law fit $\xi_{cc}=(r/r_0)^{\gamma}$ with $r_0=21.1$ Mpc h$^{-1}$and $\gamma =-1.9$ consistent with the results of $R \ge 1$ Abell clusters. We also analyze $\xi_{cc}(r)$ for subsamples defined by different X-ray luminosity thresholds where we find a weak tendency of larger values of $r_0$ with increasing X-ray luminosity although with a low statistical significance. In the different subsamples analyzed we find $21 < r_0 < 35$ Mpc h$^{-1}$ and $-1.9< \gamma < -1.6$. Our analysis suggests that cluster X-ray luminosities may be used for a reliable confrontation of cluster spatial distribution properties in models and observations.Comment: Accepted for publication in Astrophysical Journa

Inflammatory and other biomarkers: role in pathophysiology and prediction of gestational diabetes mellitus

Understanding pathophysiology and identifying mothers at risk of major pregnancy complications is vital to effective prevention and optimal management. However, in current antenatal care, understanding of pathophysiology of complications is limited. In gestational diabetes mellitus (GDM), risk prediction is mostly based on maternal history and clinical risk factors and may not optimally identify high risk pregnancies. Hence, universal screening is widely recommended. Here, we will explore the literature on GDM and biomarkers including inflammatory markers, adipokines, endothelial function and lipids to advance understanding of pathophysiology and explore risk prediction, with a goal to guide prevention and treatment of GDM.Sally K. Abell, Barbora De Courten, Jacqueline A. Boyle and Helena J. Teed

Modeling of Covalent Bonding in Solids by Inversion of Cohesive Energy Curves

We provide a systematic test of empirical theories of covalent bonding in solids using an exact procedure to invert ab initio cohesive energy curves. By considering multiple structures of the same material, it is possible for the first time to test competing angular functions, expose inconsistencies in the basic assumption of a cluster expansion, and extract general features of covalent bonding. We test our methods on silicon, and provide the direct evidence that the Tersoff-type bond order formalism correctly describes coordination dependence. For bond-bending forces, we obtain skewed angular functions that favor small angles, unlike existing models. As a proof-of-principle demonstration, we derive a Si interatomic potential which exhibits comparable accuracy to existing models.Comment: 4 pages revtex (twocolumn, psfig), 3 figures. Title and some wording (but no content) changed since original submission on 24 April 199