Transient Local Bone Remodeling Effects of rhBMP-2 in an Ovine Interbody Spine Fusion Model

Background: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a powerful osteoinductive morphogen capable of stimulating the migration of mesenchymal stem cells (MSCs) to the site of implantation and inducing the proliferation and differentiation of these MSCs into osteoblasts. Vertebral end-plate and vertebral body resorption has been reported after interbody fusion with high doses of rhBMP-2. In this study, we investigated the effects of 2 rhBMP-2 doses on peri-implant bone resorption and bone remodeling at 7 time points in an end-plate-sparing ovine interbody fusion model. Methods: Twenty-one female sheep underwent an end-plate-sparing discectomy followed by interbody fusion at L2-L3 and L4-L5 using a custom polyetheretherketone (PEEK) interbody fusion device. The PEEK interbody device was filled with 1 of 2 different doses of rhBMP-2 on an absorbable collagen sponge (ACS): 0.13 mg (1·) or 0.90 mg (7·). Bone remodeling and interbody fusion were assessed via high-resolution radiography and histological analyses at 1, 2, 3, 4, 8, 12, and 20 weeks postoperatively. Results: Peri-implant bone resorption peaked between 3 and 8 weeks in both the 1· and the 7· rhBMP-2/ACS-dose group. Osteoclastic activity and corresponding peri-implant bone resorption was dose-dependent, with moderate-tomarked resorption at the 7·-dose level and less resorption at the 1·-dose level. Both dose (p \u3c 0.0007) and time (p \u3c 0.0025) affected bone resorption significantly. Transient bone-resorption areas were fully healed by 12 weeks. Osseous bridging was seen at all but 1 spinal level at 12 and at 20 weeks. Conclusions: In the ovine end-plate-sparing interbody fusion model, rhBMP-2 dose-dependent osteoclastic resorption is a transient phenomenon that peaks at 4 weeks postoperatively. Clinical Relevance: Using the U.S. Food and Drug Administration (FDA)-approved rhBMP-2 concentration and matching the volume of rhBMP-2/ACS with the volume of desired bone formation within the interbody construct may limit the occurrence of transient bone resorption

G28.17+0.05: An unusual giant HI cloud in the inner Galaxy

New 21 cm HI observations have revealed a giant HI cloud in the Galactic plane that has unusual properties. It is quite well defined, about 150 pc in diameter at a distance of 5 kpc, and contains as much as 100,000 Solar Masses of atomic hydrogen. The outer parts of the cloud appear in HI emission above the HI background, while the central regions show HI self-absorption. Models which reproduce the observations have a core with a temperature <40 K and an outer envelope as much as an order of magnitude hotter. The cold core is elongated along the Galactic plane, whereas the overall outline of the cloud is approximately spherical. The warm and cold parts of the HI cloud have a similar, and relatively large, line width of approximately 7 km/s. The cloud core is a source of weak, anomalously-excited 1720 MHz OH emission, also with a relatively large line width, which delineates the region of HI self-absorption but is slightly blue-shifted in velocity. The intensity of the 1720 MHz OH emission is correlated with N(H) derived from models of the cold core. There is 12CO emission associated with the cloud core. Most of the cloud mass is in molecules, and the total mass is > 200,000 Solar Masses. In the cold core the HI mass fraction may be 10 percent. The cloud has only a few sites of current star formation. There may be about 100 more objects like this in the inner Galaxy; every line of sight through the Galactic plane within 50 degrees of the Galactic center probably intersects at least one. We suggest that G28.17+0.05 is a cloud being observed as it enters a spiral arm and that it is in the transition from the atomic to the molecular state.Comment: 35 pages, inludes 12 figure

Does the worsening galactic cosmic radiation environment observed by CRaTER preclude future manned deep space exploration?

Abstract The Sun and its solar wind are currently exhibiting extremely low densities and magnetic field strengths, representing states that have never been observed during the space age. The highly abnormal solar activity between cycles 23 and 24 has caused the longest solar minimum in over 80 years and continues into the unusually small solar maximum of cycle 24. As a result of the remarkably weak solar activity, we have also observed the highest fluxes of galactic cosmic rays in the space age and relatively small solar energetic particle events. We use observations from the Cosmic Ray Telescope for the Effects of Radiation (CRaTER) on the Lunar Reconnaissance Orbiter to examine the implications of these highly unusual solar conditions for human space exploration. We show that while these conditions are not a show stopper for long-duration missions (e.g., to the Moon, an asteroid, or Mars), galactic cosmic ray radiation remains a significant and worsening factor that limits mission durations. While solar energetic particle events in cycle 24 present some hazard, the accumulated doses for astronauts behind 10 g/cm2 shielding are well below current dose limits. Galactic cosmic radiation presents a more significant challenge: the time to 3% risk of exposure-induced death (REID) in interplanetary space was less than 400 days for a 30 year old male and less than 300 days for a 30 year old female in the last cycle 23–24 minimum. The time to 3% REID is estimated to be ∼20% lower in the coming cycle 24–25 minimum. If the heliospheric magnetic field continues to weaken over time, as is likely, then allowable mission durations will decrease correspondingly. Thus, we estimate exposures in extreme solar minimum conditions and the corresponding effects on allowable durations

Radiation environment at the Moon: Comparisons of transport code modeling and measurements from the CRaTER instrument

The Cosmic Ray Telescope for the Effects of Radiation (CRaTER), an instrument carried on the Lunar Reconnaissance Orbiter spacecraft, directly measures the energy depositions by solar and galactic cosmic radiations in its silicon wafer detectors. These energy depositions are converted to linear energy transfer (LET) spectra. High LET particles, which are mainly high‐energy heavy ions found in the incident cosmic ray spectrum, or target fragments and recoils produced by protons and heavier ions, are of particular importance because of their potential to cause significant damage to human tissue and electronic components. Aside from providing LET data useful for space radiation risk analyses for lunar missions, the observed LET spectra can also be used to help validate space radiation transport codes, used for shielding design and risk assessment applications, which is a major thrust of this work. In this work the Monte Carlo transport code HETC‐HEDS (High‐Energy Transport Code‐Human Exploration and Development in Space) is used to estimate LET contributions from the incident primary ions and their charged secondaries produced by nuclear collisions as they pass through the three pairs of silicon detectors. Also in this work, the contributions to the LET of the primary ions and their charged secondaries are analyzed and compared with estimates obtained using the deterministic space radiation code HZETRN 2010, developed at NASA Langley Research Center. LET estimates obtained from the two transport codes are compared with measurements of LET from the CRaTER instrument during the mission. Overall, a comparison of the LET predictions of the HETC‐HEDS code to the predictions of the HZETRN code displays good agreement. The code predictions are also in good agreement with the CRaTER LET measurements above 15 keV/µm but differ from the measurements for smaller values of LET. A possible reason for this disagreement between measured and calculated spectra below 15 keV/µm is an inadequate representation of the light ion spectra in HETC‐HEDS and HZETRN code calculations. It is also clear from the results of this work that Vavilov distributions need to be incorporated into the HETC‐HJEDS code before it will be able to recreate the observed LET spectra measured by the CRaTER instrument. Key Points Vavilov corrections should be incorporated into simulated results The predictions of the transport codes reasonably agree with the CRaTER LET The observed LET can be used to help validate space radiation transport codesPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108081/1/swe20145.pd

A Self-Consistent Approach to Neutral-Current Processes in Supernova Cores

The problem of neutral-current processes (neutrino scattering, pair emission, pair absorption, axion emission, \etc) in a nuclear medium can be separated into an expression representing the phase space of the weakly interacting probe, and a set of dynamic structure functions of the medium. For a non-relativistic medium we reduce the description to two structure functions S_A(\o) and S_V(\o) of the energy transfer, representing the axial-vector and vector interactions. $S_V$ is well determined by the single-nucleon approximation while $S_A$ may be dominated by multiply interacting nucleons. Unless the shape of S_A(\o) changes dramatically at high densities, scattering processes always dominate over pair processes for neutrino transport or the emission of right-handed states. Because the emission of right-handed neutrinos and axions is controlled by the same medium response functions, a consistent constraint on their properties from consideration of supernova cooling should use the same structure functions for both neutrino transport and exotic cooling mechanisms.Comment: 33 pages, Te

The Fine Structure Lines of Hydrogen in HII Regions

The 2s_{1/2} state of hydrogen is metastable and overpopulated in HII regions. In addition, the 2p states may be pumped by ambient Lyman-alpha radiation. Fine structure transitions between these states may be observable in HII regions at 1.1 GHz (2s_{1/2}-2p_{1/2}) and/or 9.9 GHz (2s_{1/2}-2p_{3/2}), although the details of absorption versus emission are determined by the relative populations of the 2s and 2p states. The n=2 level populations are solved with a parameterization that allows for Lyman-alpha pumping of the 2p states. The density of Lyman-alpha photons is set by their creation rate, easily determined from the recombination rate, and their removal rate. Here we suggest that the dominant removal mechanism of Lyman-alpha radiation in HII regions is absorption by dust. This circumvents the need to solve the Lyman-alpha transfer problem, and provides an upper limit to the rate at which the 2p states are populated by Lyman-alpha photons. In virtually all cases of interest, the 2p states are predominantly populated by recombination, rather than Lyman-alpha pumping. We then solve the radiative transfer problem for the fine structure lines in the presence of free-free radiation. In the likely absence of Lyman-alpha pumping, the 2s_{1/2}-2p_{1/2} lines will appear in stimulated emission and the 2s_{1/2}-2p_{3/2} lines in absorption. Searching for the 9.9 GHz lines in high emission measure HII regions offers the best prospects for detection. The lines are predicted to be weak; in the best cases, line-to-continuum ratios of several tenths of a percent might be expected with line strengths of tens to a hundred mK with the Green Bank Telescope.Comment: 18 pages, 2 figures, accepted by ApJ, references added, typos correcte

Observation of Parity Nonconservation in Moller Scattering

We report a measurement of the parity-violating asymmetry in fixed target electron-electron (Moller) scattering: A_PV = -175 +/- 30 (stat.) +/- 20 (syst.) parts per billion. This first direct observation of parity nonconservation in Moller scattering leads to a measurement of the electron's weak charge at low energy Q^e_W = -0.053 +/- 0.011. This is consistent with the Standard Model expectation at the current level of precision: sin^2\theta_W(M_Z)_MSbar = 0.2293 +/- 0.0024 (stat.) +/- 0.0016 (syst.) +/- 0.0006 (theory).Comment: Version 3 is the same as version 2. These versions contain minor text changes from referee comments and a change in the extracted value of Q^e_W and sin^2\theta_W due to a change in the theoretical calculation of the bremsstrahulung correction (ref. 16