STEM Today

JANUARY 2015, N O 1

STEM Today

Rear Admiral Grace M. Hopper, USN Grace Brewster Murray was born on December 9, 1906 in New York City. In 1928 she graduated from Vassar College with a BA in mathematics and physics and joined the Vassar faculty. While an instructor at Vassar, she continued her studies in mathematics at Yale University, where she earned an MA in 1930 and a PhD in 1934. She was one of four women in a doctoral program of ten students, and her doctorate in mathematics was a rare accomplishment in its day.

In 1930 Grace Murray married Vincent Foster Hopper. (He died in 1945 during World War II, and they had no children.) She remained at Vassar as an associate professor until 1943, when she joined the United States Naval Reserve to assist her country in its wartime challenges. After USNR Midshipman’s School-W, she was assigned to the Bureau of Ordnance Computation Project at Harvard University, where she worked at Harvard’s Cruft Laboratories on the Mark series of computers. In 1946 Admiral Hopper resigned her leave of absence from Vassar to become a research fellow in engineering and applied physics at Harvard’s Computation Laboratory. In 1949 she joined the Eckert-Mauchly Computer Corporation as a Senior Mathematician. This group was purchased by Remington Rand in 1950, which in turn merged into the Sperry Corporation in 1955. Admiral Hopper took military leave from the Sperry Corporation from 1967 until her retirement in 1971.

Throughout her years in academia and industry, Admiral Hopper was a consultant and lecturer for the United States Naval Reserve. After a seven-month retirement, she returned to active duty in the Navy in 1967 as a leader in the Naval Data Automation Command. Upon her retirement from the Navy in 1986 with the rank of Rear Admiral, she immediately became a senior consultant to Digital Equipment Corporation, and remained there several years, working well into her eighties. She died in her sleep in Arlington, Virginia on January 1, 1992.

During her academic, industry, and military tenure, Admiral Hopper’s numerous talents were apparent. She had outstanding technical skills, was a whiz at marketing, repeatedly demonstrated her business and political acumen, and never gave up on her good ideas.

— Image Credit:United States Navy(DN-SC-84-05971)

Gap’s in NASA Human Reserach Roadmap

Can SPE radiation induce oxidative stress in the bone marrow?

Observation of radiation environment in the International Space Station in 2012-March 2013 by Liulin-5 particle telescope The ISS Liulin-5 telescope module is comprised of three silicon detectors D1, D2, and D3 (instrument shown in Fig.1).

When measurements are taken inside the phantom, the Liulin-5 particle telescope is mounted inside the largest diameter channel of the phantom (Fig. 2). The detector’s axis is along the phantom’s radius. The D1 detector is at 40 mm, D2 is at 60 mm, and D3 is at 165 mm distance from the phantom’s surface. The position of D1 and D2 in the phantom corresponds approximately to the shielding of the blood forming organs (BFOs) in the human body, while D3 is placed very close to the phantom’s center. This arrangement allows measuring the depth-dose distribution along the sphere’s radius.

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Gap’s in NASA Human Reserach Roadmap

The first stage of the Liulin-5 experiment on the ISS took place from June 2007 to June 2010, corresponding to very quiet solar conditions during the deep minimum of the 23rd solar cycle. Liulin-5 was mounted in the PIRS module of the ISS. The second stage of the Liulin-5 experiment has been conducted on the ISS since 27 December 2011 in order to obtain data for the radiation conditions during solar activity increase in the 24th cycle. From 27 December 2011 to 09 March 2013 the Liulin-5 instrument was located in the MIM1 module of the Russian Segment (RS) of the ISS. Measurements both inside and outside the phantom were performed during the second stage of the Liulin-5 experiment.

During the second stage of the Liulin-5 experiment, the telescope alternated from being located inside the phantom to outside the phantom. From 27 December 2011 to 20 May 2012 the Liulin-5 detector module was mounted inside the phantom, located behind panel 206 in the MIM1 module of the RS of ISS. Liulin-5 was located outside the phantom behind panel 205 from 21 May 2012 to 30 August 2012 and from 31 August 2012 to 11 September 2012 it was also outside the phantom, but behind panel 207 in MIM1. From 12 September 2012 to 09 March 2013 the Liulin-5 detectormodulewasmounted again inside the phantom located in the MIM1module behind panel 206.

The high time resolution (20 s in SAA and 90 s outside it) of the particle flux and the dose rate data allows for detailed mapping of their distribution along the ISS orbit. The switching between 90 s and 20 s resolution is made automatically, according to a built-in criterion based on the measured particle flux F1 in the D1 detector.

The geographical distribution of the dose rate, measured by detector D3 inside and outside the phantom, is shown in the two panels of Figure 4, where X-axis is the longitude, Y-axis is the latitude, and the dose rate intensity is color coded. Measurements taken inside the phantom for the time intervals from 27 December 2011 to 20 May 2012 and from 12 September 2012 to 09 March 2013 are shown on the upper panel of the figure. The data from measurements outside the phantom in the period 21 May to 11 September are displayed on the bottom panel. In both distributions the maximal dose rates are recorded in the region of the SAA from the trapped protons. Inside the phantom the biggest value recorded is 440.5 µ Gy h −1 , while outside the phantom the maximum dose rate in the SAA is 713 µ Gy h −1 . As can be expected the SAA region has different shape and area for the different types of measurements.

Outside the SAA the lowest doses from GCRs (0.36 µ Gy h −1 inside the phantom and 0.4 µ Gy h −1 outside it)are obtained near the equator, the highest values of 9-10 µ Gy h −1 are measured at high geographic latitudes for both inside and outside the phantom.

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Gap’s in NASA Human Reserach Roadmap

In Figure 5 the average dose rate distribution measured by detector D3 for the entire interval from 27 December 2011 to 09 March 2013 is plotted (data are averaged for periods of about 14 days). The total dose rate (black curve) and its individual contributions (GCRs (blue curve), SAA trapped protons (red curve)) are plotted separately. The picture shows that the total dose rates near the phantom’s center (130-150 µ Gy h −1 ) are about 1.7 times less than outside the phantom (200-240 µ Gy h −1 for the time interval 21 May-11 September 2012). This decrease is mainly due to the selfshielding of the phantom against the SAA trapped protons. The SAA dose rates are 120-160 µ Gy h −1 outside the phantom and 50-70 µ Gy h −1 near the center of the phantom. The GCR dose rates are 70-85 µ Gy h −1 (about 1.2 times the maximal difference). The lowest values of the GCR dose rate are in July-August 2012 (when the detector module was located outside the phantom).

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Gap’s in NASA Human Reserach Roadmap

In 2012 a number of SEP events occurred (23 January, 27 January, 07 March, 13 March, 17 May, 27 May, 16 June, 07 July, 12 July, 17 July, 01 September, 28 September), for which GOES proton > 10 MeV flux exceeded the threshold of 10 part cm −2 s−1 sr−1 .

However, only the event of March 07 led to significant changes in the radiation environment inside the ISS. Below, the radiation quantities from the Liulin-5 investigations during these SEP events are discussed and the data are also compared to those during undisturbed radiation conditions.

A typical distribution of Liulin-5 particle flux and dose rate data as a function of the L-value is presented in the upper scatterplot of Figure 6 taken from Semkova et al.(2013c).The data represent the measurements in detector D1 at 40 mm depth into the phantom during quiet radiation conditions, about 11 h after the end of the SEP events observed on the ISS orbit in March 2012 (see Table 2). The two main sources of radiation in LEO (GCRs and the trapped protons of the inner radiation belt in the SAA) are well seen. At L-values 1.1-2 both sources contribute to the measured flux. Maximal fluxes of 19.3 part cm −2 s−1 are registered from the trapped protons in the SAA at L ≈ 1.24. The maximum dose rate in the SAA was 370 µGy h−1 . Minimal values of about 0.035 part cm −2 s−1 were recorded at L ≈ 1 from GCR. Outside the SAA the averaged flux from GCR was 0.2 part cm −2 s−1 , the averaged absorbed dose rate 2.65 µGy h−1 . At L > 3 the GCR flux was about 0.7 part cm −2 s−1 , the dose rate was about 9.5

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Gap’s in NASA Human Reserach Roadmap µGy h−1 .

On 07 March 2012 GOES-13 registered the beginning of two SEP events (proton fluxes with energy ≥ 10 MeV exceeding the threshold of 10 part cm −2 s−1 ) at geosynchronous orbit. A greater than 100 MeV event began at 04:05 UT on 07 March 2012, reached a maximum of 69 part cm −2 s−1 at 15:25 UT the same day, and ended at 16:50 UT on 10 March 2012. Also, a greater than 10 MeV event began at 05:10 UT on 07 March 2012, reached a maximum of 6530 part cm −2 s−1 at 11:15 UT on 08 March 2012, and ended at 20:50 UT on 12 March 2012.The SEP events were associated with Earth-directed CMEs.During these SEP events the Liulin-5 detector module was located inside the phantom.The first registration of the particle flux and dose rate increase in Liulin-5 data was on 07 March 2012, at 13:01 UT, at L = 3,latitude = -42.3 ◦ , longitude = 136.6◦ , altitude = 415.26 km.

The increase of the particle flux and dose rates at L > 3 is observed in all three detectors of Liulin-5 located at 40, 60, and 165 mm depths along the radius of the spherical phantom.In the middle scatterplot of Figure 6 the

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Gap’s in NASA Human Reserach Roadmap distribution of the particle flux and the dose rate in the D1 detector of Liulin-5 (at 40 mm depth in the phantom) as a function of L-value for the time interval 07-09 March 2012 is presented. The comparison with the data during quiet conditions (upper scatterplot) shows that there is no increase of the dose rate and particle flux in the region of the SAA during the SEP events. The maximum flux observed outside the SAA during those SEP events reached 7.2 part cm −2 s−1 and the dose rate reached 107.8 µGy h−1 on 07 March 2012, 13:06 UT at L = 4, latitude = -51.1◦ ,longitude = 166.8◦ , altitude = 422 km. These values are about 10 times larger than the common GCR dose rates and fluxes at high latitudes.

Another SEP event occurred on 17 May 2012, associated with the M5 solar flare the same day: at 02:10 UT a greater than 10 MeV event began with a maximum of GOES proton flux of 255 part cm −2 s−1 registered on 17 May at 04:30 UT and a greater than 100 MeV proton event began at 02:00 UT and reached a maximum of 20 part cm −2 s−1 at 02:30 UT, ended at 17:25 UT the same day.

In the bottom scatterplot of Figure 6 the distribution of the particle flux and the dose rate in the D1 detector of Liulin-5 as a function of the L-value for the time interval 14-20 May 2012(measurements taken at 40 mm depth in the phantom) is presented. A slight increase of the dose rate and the particle flux is observed on 17 May since 09:50 UT to 15:16 UT. The maximum flux was 1.15 part cm −2 s−1 and the dose rate reached 14.2 µGy h−1 on 17 May 2012, 09:55 UT at L = 4.8, latitude = -51.3◦ , longitude = 151◦ , altitude =413 km.

In Table 2 the averaged dose rates, quality factors, and dose equivalent rates at 40 mm depth in the phantom obtained outside the SAA during the March 07 and May 17 SEP events, as well as data during quiet radiation conditions before the May 17 SEP event are presented. The table shows that the averaged dose and dose equivalent rates during the March 07 SEP event are higher than the values during non-disturbed conditions. The total additional

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Gap’s in NASA Human Reserach Roadmap absorbed dose received from the solar energetic particles was about 180 µGy, thus the additional dose equivalent was approximately 448 µSv. These values are comparable to the daily absorbed dose and dose equivalent at that depth during quiet periods in 2012.

It is also evident that the averaged dose rate, quality factor, and dose equivalent rate obtained outside SAA during the May 17 SEP event are comparable to those during the quiet period before the SEP event and that the radiation conditions in the phantom were practically not affected by the May 17 SEP event.

In the upper plot of Figure 7 the proton flux F with energies ≥ 100 MeV measured by GOES-13 from 07 to 10 March 2012 is shown (blue curve). The dose rate in the D1 detector of Liulin-5 measured outside SAA, and the corresponding L-values are plotted versus time for the period from March 07, 07:00 UT to March 10, 00:00 UT, 2012.

It is seen that the trend of the Liulin-5 dose rate during that period of the SEP events corresponds to the trend of the proton flux with energies above 100 MeV (the main contribution to the fluxes and doses by Liulin-5 detectors inside the phantom in ISS is from protons of energies above 100 MeV outside ISS). After March 09, 06:00 UT the GOES ≥ 100 MeV proton flux is less than 10 part cm −2 s−1 and the Liulin-5 dose rate goes down to its almost normal values of about 10 µGy h−1 at L > 3.

In the bottom plot of Figure 7 the proton flux F with energies ≥100 MeV measured by GOES-13 is shown (blue curve).The dose rate in the D1 detector of Liulin-5 measured outside the SAA, and the corresponding L-values are plotted versus time for the period from May 17, 00:00 UT toMay 20, 00:00 UT, 2012. Again the trends of the Liulin-5 dose rate and the proton flux with energies above 100 MeV during that SEP event are similar. The picture shows that when the GOES proton flux with energies greater than 100 MeV reached maximum of about 20 part cm −2 s−1 at 04:30 UT, the ISSwas at the lowLvalues part of its orbit.When the ISS orbit entered high L values, the GOES > 100 MeV protonfluxwas already below 3 part cm −2 s−1 .Because of that the dose rate and the particle flux in the ISS did not increase significantly during that SEP event and the SEP event did not affect practically the radiation conditions in the spherical phantom.

During 2012 there were 11 more SEP events for which GOES proton > 10 MeV flux exceeded the threshold of 10 part cm −2 s−1 . In three of them - those on 27 May, 16 June, and 01 September there was no change in the GOES proton > 100 MeV flux. During 5 SEPs (on 13 March, 07 July, 12 July, 17 July, and 28 September) the GOES proton fluxwith energies greater than 100 MeV showed either a slight enhancement or a slight increase. On 23 January 2012 STEM Today Page 9

Gap’s in NASA Human Reserach Roadmap the GOES proton > 100 MeV flux reached only 2 part cm −2 s−1 . During the SEP on 27 January the GOES proton > 100 MeV flux increased for about 2 h around 21 UT, but the flux was weak -22 part cm −2 s−1 at maximum and the ISS was at very low L-values.Thus all these SEP events did not affect significantly the Liulin-5 data either due to the L value location or due to the intensity of the SEPs. The dosimeter-radiometer Liulin onboard the Mir space station was designed for measuring the absorbed dose and flux of penetrating particles using a silicon detector 300 µ m thick and 2 cm 2 area. The device was located in the work section of the space station where the estimated mean mass shielding was about 6-15 g cm−2 , therefore the main contribution to the device readings was made by electrons and protons with energies outside of the station respectively Ee > 10 MeV, and Ep > 100 MeV. Liulin was in active operation on Mir from 1989 to 1994. Liulin has collected data about the radiation environment during a number of SEP events in September-October 1989, March 1991, June 1991, and June 1992.

During the measurements in September-October 1989, the Mir space station orbit was at altitude 380-420 km and inclination 51.6◦ . During the SEP event on 29-30 September 1989 (a solar flare of X9.8 importance) when the space station reached high latitudes in the near-polar geomagnetic regions (L > 3.5) the dose rate and the flux showed a sharp rise up to 2 mGy h−1 and 150 cm −2 s−1 , respectively. The flux exceeded 150 times and the dose rate exceeded 500-600 times the common values for those regions in the absence of SEPs. In the upper plot of Figure 8 the flux, absorbed dose rate, and ratio absorbed dose/flux measured by the D1 detector of Liulin-5 on ISS during the SEP event on 07 March 2012 from 17:20:08 UT to 17:46:30 UT are plotted versus L value. In the bottom plot of Figure 8 are plotted the same parameters obtained by the Liulin dosimeter on Mir space station during the SEP event on 30 September 1989 from 00:54:10 UT to 01:18:40 UT. The data in both plots are taken outside the SAA. Comparing the results of Liulin on the Mir space station for the SEP event on 29-30 September 1989 with those of Liulin-5 on the ISS for the SEP event on 07 March 2012 it is evident, that the SEP effect on the Mir radiation environment was much more dramatic than that on the ISS environment.

Several facts contribute to that difference: (1)During the SEP event on 29-30 September 1989, when the sharp enhancement in the Liulin data was registered, the GOES proton flux with energies > 100 MeV was 250 cm2 s1, about five times larger than in the 07 March 2012 event at 13:06 (the maximum in Liulin-5 data) when it was 50 cm−2 s−1 ; (2) The two instruments were behind different shielding: the shielding for Liulin on Mir is evaluated to be 6-15 g cm−2 ; that of Liulin-5 on the ISS, when it was in the PIRS module, was 2-20 g cm−2 for D1. Our estimations show that the shielding for Liulin-5 while it is in the phantom behind panel 206 in the MIM1 module is greater than in the PIRS module; (3)Another cause for the difference could be the different energy spectrum of the SEP events.

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Gap’s in NASA Human Reserach Roadmap

The radiation environment on the ISS is observed also by the detectors DB8 of the radiation monitoring system (RMS) since August 2001. DB8 is a set of four identical units. Each of the units consists of two silicon detectors. The area of each detector is 1 cm 2 and the thickness is 300 µm. One of the detectors inside each DB-8 unit is protected by a sphere of lead surrounding the detector. The thickness of the lead sphere is 2.5 mm (3 g cm −2 ). The four DB8 units are located behind different shielding in different points inside the ISS Service module. Thus the RMS provides monitoring of the dose rate dynamics in a few points of the ISS Service module. The shielding of DB-8 detectors is 1-600 g cm −2 (least shielded) and 6-600 g cm −2 (most shielded). During the maximum of the 23rd solar cycle(2001-2004) four SEP events were monitored (24 September 2001, 04 November 2001, 28 October 2003, and 30 October 2003). The absorbed doses and dose equivalents during those events differ in different points depending on the shielding.

The largest values were obtained during the SEP event that started on 28 October 2003, when the minimal absorbed dose and dose equivalents were, respectively, 600 µGy and 1.1 mSv at the most shielded point, maximal values reached 6.6 mGy and 12 mSv at the least shielded point. Model extrapolations made by the authors predict 2.6 mSv dose equivalent to the BFOs in the Service module of ISS during that SEP event. For comparison during the SEP event of 07 March 2012 the minimal absorbed dose measured by DB8 was 550 µGy at the most shielded point and 1.84 mGy at the least shielded shielded point.

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Gap’s in NASA Human Reserach Roadmap The SEP event on 28 October 2003 had a proton flux with energies >100 MeV 100-200 cm −2 s−1 , and is thus 2-4 times more than the SEP event on 07 March 2012. The shielding of the Liulin-5 detectors during the March 2012 event is greater than that of the most shielded DB-8.The total dose equivalent of the D1 detector of Liulin-5 (shielding approximately as that of BFO in MIM1) from the SEP event on 07 March 2012 is 0.45 mSv and is thus 5.8 times less than the model extrapolation in Benghin et al. (2005) for the SEP event on 28 October 2003.

The space radiation environment inboard is measured by Area PADLES dosimeters at 17 places in the Japanese Experiment Module "KIBO".

• 12 places in Pressurized Module (PM)(It is four places in the Node side, the Exposed Facility (EF) side, and the center for each.)

• 5 places in Experiment Logistics Module-Pressurized Section(ELM-PS)(zenith and four places in Pressurized Module (PM) joint part) These Area PADLES dosimeters are collected and changed in every approximately 6-8 months (1-2 times a year), and are analyzed in Tsukuba space center after the return.

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Gap’s in NASA Human Reserach Roadmap

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Gap’s in NASA Human Reserach Roadmap

Bio PADLES dosimeters can be installed in various temperature environments (for example, minus 80 degree Celsius in the MELFI refrigerator, and 37 degree Celsius in the Cell Biology Experiment Facility (CBEF)).

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Gap’s in NASA Human Reserach Roadmap

Ionizing Radiation and Bone Loss Recent animal models are now beginning to demonstrate that spaceflight-relevant doses and qualities of radiation represent a risk to skeletal health due to an acute increase in bone resorption followed by the suppression of bone formation Skeletal unloading, due to extended periods of bed rest or the reduced gravity environment of space , is a well-known cause of bone loss in both humans and rodent models . Unloading-induced bone loss is characterized by both increased bone resorption and decreased bone formation. This stands in contrast to traditional postmenopausal osteoporosis, which sees bone resorption and formation moving in parallel, albeit with the former increasing to a relatively greater degree. The combination of microgravity unloading and spaceflight radiation may interact to enhance bone loss .

Effects of Radiation on Bone Mineral Density of Radiology Workers Depending on The Device They Use 49 radiology workers (technicians) of total 55 ,which were volunteer for the study, exposed to ionizing and nonionizing radiation due to their profession in Kutahya’s state and private hospitals are chosen as working group. Technicians use lead wear and barrier while working as a protection method. The quantity of radiation, radiology workers were exposed to in last one year, is measured by TAEK (Turkey Atomic Energy Instute) by means of using individual TLD (Thermoluminescence Dosimetry). It was measured 4,8 mSv at average.

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Gap’s in NASA Human Reserach Roadmap Table 1 shows characteristics of subjects. The control group have been working in the same hospital’s radiology departments with working group, but control group has not exposed to radiation. Additionally, these people haven’t been exposed to any diagnostic and therapeutic irradiation in the last one year.

After the first measurements of radiation, there was no radiation both in control rooms and radiation working rooms. It was found out that radiation stays 22 seconds at the room after irradiation and technicians leave from lead barriers at the first 3 seconds. Conventional roentgen workers, while working, are exposed to radiation between the doses of 0,0031 mSv and 0,15 mSv. In tomography, seconder radiation is between 0,57 mSv and 1,3 mSv after every irradiation (Table 2).

According to DEXA results, the working group was compared to control group regarding the device they use.T-scores of radiology workers, in all groups, were lower than control group meaningfully (p<0.01). Moreover, T-scores of MRI workers were lower than conventional roentgen workers meaningfully (p<0.01). T-scores of tomography workers were lower than conventional roentgen workers and it was higher than MRI workers but there was no statistically significant difference among the groups (P>0.05). MRI<Tomography< Conventional roentgen < Control (Table 3).

Depending on sex, if we compare according to the device they use, T-scores of radiology workers (all groups) were meaningfuly lower for both women and men than the control group (P < 0.01). In working group comparision among themselves, it is found that MRI workers have the lowest T-scores and conventional roentgen workers have the highest T-scores for both women and men. It was also found out that T-scores of the men at the control group were higher than the women’s however the case was just the opposite for the work group (Table 4). Regarding the device they use, serum ALP levels of roentgen and tomography workers were lower than the control group meaningfully (p<0.05). Serum ALP levels of MRI workers were lower than the control group but there was not any meaningful difference on MRI workers (p>0.05)(Table 5).

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Gap’s in NASA Human Reserach Roadmap

Exposures to low dose ionizing radiation and non-ionizing radiation have significant decreasing effect on bone mineral density of radiology workers. Likewise, exposures to low dose ionizing radiation have noteworthy decreasing effect on serum alkaline phosphatase levels of them.

Bone Architectural and Structural Properties after 56 Fe +26 Radiation-Induced Changes in Body Mass During missions outside the magnetosphere, astronauts will be exposed to charged-particle species from all stable elements (hydrogen, helium, carbon, oxygen and iron are considered the most important). Protons make up approximately 87% of the fluence of galactic cosmic radiation, which is present at an essentially constant low dose rate approximately 100-fold greater than at the Earth’s surface. Additionally, unpredictable solar particle events can deliver high doses of proton radiation: as much as 3Gy over a period of hours to days. However, the health risks from heavy-ion radiation may be even greater. Highenergy 56 Fe +26 ions are of particular interest because their dense tracks of ionization result in high relative biological effectiveness (RBE), which is associated with concentrated, poorly repairable damage within organisms. Production of secondary fragments by 56 Fe +26 ions is also of concern.

Bone damage occurs after direct exposure to low-linear energy transfer (LET) ionizing radiation ( γ and X rays) and is thought to be a result of physiological changes that occur to both vasculature and bone cells, primarily boneforming osteoblasts.

Previous studies suggest that bone-resorbing osteoclast numbers tend to decrease after carbonion (HZE) irradiation. Bone loss at 4 months has been documented in mice whole-body irradiated with low-and high-LET radiation , and clinical studies have demonstrated an increased risk of fractures after radiotherapy. Therefore, deterioration has been observed in directly irradiated bone.

Forty 9-week-old male Sprague-Dawley rats (Harlan, Indianapolis, IN) were shipped directly from the vendor to Brookhaven National Laboratory (BNL) and acclimatized for 1 week. All protocols were approved by the Institutional Animal Care and Use Committees at BNL and Loma Linda University (LLU). Rats were given access to food and water ad libitum and kept in a temperature-controlled (18-26◦ C) and light-controlled (12-h light/dark cycle) environment. Thirty rats were selected randomly for radiation exposure and placed into treatment groups, while 10 control rats were not exposed to radiation.

The experiment was part of NASA-funded experimental collaboration BNL-9 in November 2002. The primary radiation was 5 GeV/µm 56 Fe +26 ions delivered at dose rate of approximately 1.5 Gy/min as 18 0.5-s spills per minute. The track-averaged LET for the particles was approximately 143 keV/µm.

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Gapâ&#x20AC;&#x2122;s in NASA Human Reserach Roadmap Animal mass for all treatment groups was less than control- group mass at 9 months post irradiation (Table 1),though the difference for the 2-Gy group was not significant.Individual animals in the 1-Gy and 4-Gy groups were significantly smaller than control, having approximately 10% and 19% less mass, respectively (P < 0.001). No differences in tibial mass were observed between groups. Femoral mass for the 4-Gy group was significantly different from the control ( â&#x2030;&#x2C6; 10% smaller; P < 0.05).

The percent mineralization was calculated for (a) the proximal epiphysis, diaphysis and whole tibia and (b) the head, proximal epiphysis, diaphysis and whole right femur from each rat. No changes were observed in the percent mineralization of any specific site within the bones or between the whole bones of the different groups. Only wholebone mineralization data are reported (Table 1).

Trabecular bone volume fractions within the proximal epiphysis were significantly less than the control in the 2and 4-Gy groups by approximately 20% (P < 0.05) and 26% (P < 0.01), respectively, when compared using ANOVA (Fig. 2). The connectivity density of trabeculae within the epiphyses was also significantly reduced after the higher doses (Fig. 2). Trabecular connectivity for the 2- and 4-Gy groups was 32% and 28% less than control, respectively(P < 0.05). Trabecular thickness was significantly lower in the 4-Gy group than in the control and 1-Gy groups (P < 0.05). No differences were observed in trabecular number or separation (Table 1, Fig. 2).

Significant radiation effects were reported for trabecular bone volume fraction, connectivity and thickness, after testing the variables with an ANCOVA, that accounted for final animal mass (Table 2). Bone volume fraction was significantly lower in the 2-Gy group compared with the control and 1-Gy groups (P < 0.05). Likewise, connectivity from 2-Gy animals was significantly less than from control and 1-Gy animals (P < 0.05). Animals in the 2-Gy group were larger than in other treatment groups (Table 1), and thus the lower trabecular bone volume fraction and connectivity relative to nonirradiated controls remained significant despite the final size of the individual animals.

After accounting for mass, no differences were observed in trabecular number and separation. However, trabecular thickness for the 4-Gy group was significantly less than for all other groups even after adjusting for body mass (P < 0.05).

The diaphyses of the scanned tibiae were analyzed for changes in cortical parameters using absolute means (Table 1) and adjusting for final animal mass (Table 2). Comparing absolute means, the volume of cortical bone located approximately 0.5 mm proximal to the tibial-fibular junction was significantly decreased (P < 0.01) from the control in animals irradiated with 1 Gy (-9.5%) and 4 Gy (-8.1%) (P < 0.05) 56 Fe-particle radiation. pMOI was significantly smaller at this location in the 1-Gy (-19%, P < 0.01) and 4-Gy (-14%, P = 0.05) groups (Table 1). However, all differences became insignificant when accounting for body mass (Table 2). Cortical porosity was unchanged in the irradiated diaphyses.

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Gapâ&#x20AC;&#x2122;s in NASA Human Reserach Roadmap

Table 3 summarizes the bone turnover markers from plasma. Tartrate-resistant acid phosphatase (TRAP), a biochemical indicator of bone resorption, was significantly elevated in the 1-Gy group over control levels by approximately 35% (P < 0.05). No differences were observed in the concentrations of the other indicators of bone metabolism (i.e., alkaline phosphatase, osteocalcin, calcium or phosphorus) in irradiated groups.

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Gapâ&#x20AC;&#x2122;s in NASA Human Reserach Roadmap

Exposure to 56 Fe +26 radiation has a negative impact on bone microarchitecture and structure in rats even when hind limbs are excluded from the radiation beam. Compared to controls, irradiated animals exhibited less trabecular bone volume fraction, connectivity and thickness after exposure to doses greater than 2 Gy. These changes in bone parameters were largely related to final animal body mass. Indicators of bone metabolism (mineral content, cortical porosity, serum protein analyses) were generally unchanged, suggesting stabilized bone turnover at 9 months.

Therefore, the reduction in bone volume and impaired microarchitecture are likely permanent adaptations.

Exposure of rodents to 56 Fe +26 -ion radiation resulted in reduced trabecular bone microarchitecture and volume within the proximal tibia, a bone not directly exposed to 56 Fe +26 ions. The changes seem to be associated with the lower body masses of irradiated individuals, though the cause of the reduced body mass (or any systemic factors resulting in loss of bone) could not be determined. Insight into the effects of 56 Fe +26 -ion and particulate irradiation on bone may be important to the health of astronauts on future long-duration space flights (e.g. Mars).

Effect of proton irradiation followed by hindlimb unloading on bone in mature mice: A model of long-duration spaceflight During extended missions, astronauts will also be exposed to both solar and cosmic radiation. Due to the shielding effect of the Earthâ&#x20AC;&#x2122;s magnetosphere, the type and dose of radiation encountered will be significantly different than those experienced on the ISS, which is located in low Earth orbit. Multiple spaceflight-relevant types of radiation have been documented as having negative effects on trabecular bone. For Mars missions, cosmic rays (containing heavy ions and protons) and solar particle events (SPEs; composed mainly of protons) are the primary concern for radiation exposure. SPEs occur randomly and can deliver a relatively high dose (up to 2 Gy) over a short period of time.

Although spacecraft shielding can effectively reduce radiation exposure, the warning provided by current surveillance mechanisms may not allow for complete protection during extravehicular activities. Even if astronauts were sheltered behind a mass of 5 g/cm2 (e.g., 1.9 cm of aluminum or 5 cm of water), severe SPEs, such as those observed in August 1972 and October 1989, could deliver whole-body radiation doses approaching 2 Gy. Given the duration of future missions planned by NASA to nearby asteroids and Mars, a dose of approximately 1 Gy proton radiation is a realistic possibility and should be used to develop mission-safety protocols. Previous studies in our laboratory have demonstrated significant, long-term loss of trabecular microstructure at multiple sites following doses as low as 1 Gy protons or 2 Gy X-rays.

Female C57BL/6 mice (Taconic Farms; Germantown, NY) were shipped to the Loma Linda University Medical Center (Loma Linda, CA) at fifteen weeks of age and acclimatized for 1 week under standard vivarium conditions. Animals were grouped by mass (5 groups, n=15-17/group). A detailed description of the treatment groups is presented in Table 1. All mice were provided with standard laboratory rodent chow and water ad libitum. All animal procedures were approved by the Institutional Animal Care and Use Committee at both Loma Linda University and Clemson University (Clemson, SC).

Two groups of animals were irradiated (IRR), while the remaining experimental animals were subjected to a sham irradiation procedure (i.e., non-irradiated controls; NR).One day after the irradiation or sham procedure, one half of STEM Today Page 20

Gap’s in NASA Human Reserach Roadmap the IRR mice and one half of the NR mice were subject to hindlimb suspension (HLS). The remaining mice were kept as normally loaded controls (LC). This allocation produced the following five groups: baseline (BSL), non-irradiated and normally loaded (NR+LC), irradiated and normally loaded (IRR+LC), non-irradiated and hindlimb suspension (NR+HLS), and irradiated and hindlimb suspension (IRR+HLS)(Table 1).

Mean animal mass at sacrifice for each group was as follows: BSL= 22.4± 0.27 g, NR + LC=23.2±0.32 g, IRR + LC=23.3±0.38 g, NR + HLS=22.6±0.30 g, and IRR + HLS=22.4±0.30 g. There was no significant effect of irradiation on animal mass. Overall, HLS mice were 3-4% lighter than LC mice. However, these differences were not significant when comparing individual groups (i.e., NR + HLS versus NR+LC and IRR + HLS versus IRR + LC).

Compared to 20 week-old NR+LC, 16-week-old baseline mice(BSL) had higher trabecular BV/TV as well as higher overall trabecular bone quality in both the proximal tibia (Fig. 1) and the distal femur (Fig. 2), as represented by higher trabecular bone parameters including Conn.D, Tb.N, Tb.Sp, and SMI.

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Compared to NR + LC, IRR + LC mice experienced significant deterioration of trabecular microarchitectural parameters. In the proximal tibia, IRR + LC mice had significantly lower BV/TV (-16%), Conn.D (-28%), and Tb.N (-7.7%) and significantly higher Tb.Sp (+9.0%) and SMI (+11%) (Fig. 1). In the distal femur, IRR+LC had significantly lower BV/TV (-22%) and Conn.D (-37%) and higher SMI (+8.0%) (Fig. 2). Tb.N and Tb.Sp were unchanged.

In both the tibia and femur, cortical bone parameters, including Ct.TV, Ct.BV, Ct.Po, and pMOI were not different between IRR + LC and NR + LC (Table 2). Similarly, femurs from IRR+LC mice did not have significantly different mechanical strength or any mechanical parameters assessed when compared to NR+LC (Fig. 3).

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Percent mineralization in the femur was not significantly different between IRR + LC and NR + LC (Fig. 4). Serum markers of bone turnover, including osteocalcin and TRAP5b, were also not different between IRR+LC and NR+LC (Table 3). In addition, histological parameters, including ES(Oc+)/BS, ES(Oc-)/BS, Oc.S/BS, and N.Oc/BS, were not significantly different between IRR + LC and NR + LC mice (Table 3).

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Compared to NR+LC, NR+HLS mice experienced substantial deterioration of trabecular bone. At the proximal tibia, NR + HLS mice were found to have significantly lower trabecular BV/TV (-74%), Conn.D (-86%), Tb.N (-22%), and higher Tb.Sp (+29%) and SMI(+45%) (Fig. 1). There were similar findings in the trabecular bone of the distal femur, where NR+HLS mice had significantly lower BV/TV (-60%), Conn.D (-75%), and Tb.N (-12%) and higher Tb.Sp (+14%) and SMI (+7.3%) compared to NR+LC (Fig. 2).

As opposed to irradiated mice, NR + HLS mice experienced significant loss of cortical microstructure when compared to NR + LC (Table 2). In the proximal tibia, these mice had significantly lower Ct.TV (-19%), Ct.BV (-23%), and pMOI (-18%), and higher Ct.Po (+34%). In the distal femur, NR+HLS mice had significantly lower Ct.TV (21%), Ct.BV (-24%), pMOI (-21%), and higher Ct.Po (+33%) versus NR + LC. NR + HLS mice also had reduced mechanical competency compared to NR + LC, with significantly reductions in stiffness, maximum force, and elastic force (Fig. 3). Percent mineralization was lower in both the epiphysis and diaphysis in NR + HLS versus NR + LC mice (Fig. 4).

NR + HLS mice did not have significantly different levels of the bone formation marker osteocalcin when compared to levels in NR + LC (Table 3). However, NR+HLS mice did have significantly higher levels of the bone resorption marker TRAP5b when compared to NR + LC. Histological examination of the proximal tibia did not reveal any significant differences between NR + HLS and NR + LC mice in terms of Oc.S/BS or N.Oc/BS. Overall, HLS mice had higher ES(Oc+)/BS and ES(Oc-)/BS. However, these differences were not significant when individual groups were compared (i.e., NR + HLS versus NR + LC mice).

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Gapâ&#x20AC;&#x2122;s in NASA Human Reserach Roadmap Compared to NR + HLS, IRR + HLS mice had deteriorated trabecular microarchitecture. In the tibia, IRR + HLS mice had significantly lower Conn.D (-38.9%) and Tb.N (-8.0%) and significantly higher Tb.Sp (+9.6%) and SMI (+9.6%) when compared to NR+HLS (Fig. 1). There was a trend of decreased BV/TV (-17.4%; P=0.053) in IRR + HLS mice compared to NR+HLS (Fig. 1). A statistically significant interaction between radiation and unloading was present for Conn.D in the tibia. In the femur, IRR+HLS mice had significantly lower BV/TV (-26.4%) and Conn.D (-45.9%) and significantly greater SMI (+7.4%) versus NR + HLS (Fig. 2).

In the femur, Tb.Sp and Tb.N were not significantly different between IRR + HLS and NR+HLS mice. The percent differences between irradiated and non-irradiated animals were similar for both the LC and HLS mice for several trabecular microarchitectural parameters in both the tibia and the femur (Table 4).

In both the tibia and femur, cortical bone parameters (including Ct.TV, Ct.BV, Ct.Po, and pMOI) were not different between IRR+HLS and NR + HLS mice (Table 2). Similarly, IRR + HLS did not have significantly different measures of mechanical strength when compared to NR+HLS (Fig. 3). While mineral content in the diaphysis of the femur was not significantly different, IRR+HLS mice had lower mineral content in the epiphysis and overall compared to NR + HLS (Fig. 4).

A statistically significant interaction between radiation and unloadingwas present for mineral content in the epiphysis and total femur. Markers for bone turnover, including osteocalcin and TRAP5b, were not significantly different between IRR + HLS and NR + HLS mice (Table 3). In addition, therewas no significant difference in histological parameters, including ES(Oc+)/BS, ES(Oc-)/BS, Oc.S/BS, and N.Oc/BS, when comparing IRR + HLS and NR + HLS mice.

1 Gy of whole body proton irradiation results in significant loss of trabecular bone at the proximal tibia.the effect of radiation on bone is not specific to one site. Previous studies from our laboratory have demonstrated bone loss in mice four months after proton radiation exposure . Here, we report a similar amount of bone loss in the tibia (â&#x2030;&#x2C6; 15%) just one month after irradiation. This similarity suggests that the deterioration of bone resultant from 1 Gy of radiation is persistent long after exposure.

These findings may have significant implications for the recovery of astronauts following spaceflight radiation exposure as a prolonged period of compromised bone structure may increase the risk of fracture during a mission or following return to Earth. Models predicting recovery of skeletal sites such as the lumbar spine, pelvis, and calcaneus following 4-6 month missions on the ISS suggest that it would take nine months to regain 50% of the BMD lost during spaceflight. Indeed, direct measurements on astronauts following long duration missions have shown that proximal femur bone mineral density (BMD) and calculated bone strength were only partially recovered a year after return to Earth . It is clear that the recovery period is much longer than the actual period of spaceflight exposure and, as we have shown, exposure to types and doses of radiation found outside of low Earth orbit may further comprise bone structure and delay recovery.

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Gapâ&#x20AC;&#x2122;s in NASA Human Reserach Roadmap Reference: 1.Semkova, J., T. Dachev, R. Koleva, N. Bankov, S. Maltchev, et al. Observation of radiation environment in the International Space Station in 2012-March 2013 by Liulin-5 particle telescope. J. Space Weather Space Clim., 4, A32, 2014,DOI: 10.1051/swsc/2014029.

2.Di Fino L, Zaconte V, Stangalini M, Sparvoli R, Picozza P, et al.: Solar particle event detected by ALTEA on board the International Space Station. J. Space Weather Space Clim., 2014, 4, A19.

3.Baker, D. N., X. Li, A. Pulkkinen, C. M. Ngwira, M. L. Mays, A. B. Galvin, and K. D. C. Simunac (2013), A major solar eruptive event in July 2012: Defining extreme space weather scenarios, Space Weather, 11, 585-591, doi:10.1002/swe.20097.

4.Ngwira, C. M., A. Pulkkinen, M. L. Mays, M. M. Kuznetsova, A. B. Galvin, K. Simunac, D. N. Baker, X. Li, Y. Zheng, and A. Glocer (2013), Simulation of the 23 July 2012 extreme space weather event: What if this extremely rare CME was Earth directed?, Space Weather, 11, 671-679, doi:10.1002/2013SW000990.

5.Ying D. Liu, J. G. Luhmann, P. Kajdic, E. K.J. Kilpua, N. Lugaz, N. V. Nitta, C. Mostl, B. Lavraud, S. D. Bale, C. J. Farrugia, and A. B. Galvin, Observations of an extreme storm in interplanetary sp.ace caused by successive coronal mass ejections, Nature Communications, 18 March 2014, doi: 10.1038/ncomms4481 6.Solar Monitor (http://solarmonitor.org/full_disk.php?date=20120307&type=saia_00193&indexnum=1) 7.Helioviewer (http://bit.ly/1Job3J6) 8.Daniel N. Baker,A Major Solar Eruptive Event in July 2012: Defining Extreme Space Weather Scenarios (http://www.swpc.noaa.gov/sites/default/files/images/u33/Baker_July2012_SWW.pdf) 9.Semkova, J., T. Dachev, R. Koleva, S. Maltchev, N. Bankov, V. Benghin, V. Shurshakov, V. Petrov, and S. Drobyshev. Radiation environment on the international space station during the solar particle events in March 2012. Astrol. Outreach, 1, 102, 2013c, DOI: 10.4172/2332-2519.1000102.

10.Halil Kunt, Hayri Dayioglu,The Effects of Radiation on Bone Mineral Density of Radiology Workers Depending on The Device They Use,Eur J Gen Med 2011;8(4):318-322.

11. Willey, J. S., Grilly, L. G., Howard, S. H., Pecaut, M. J.,Obenaus, A., Gridley, D. S., Nelson, G. A. and Bateman, T. A.Bone Architectural and Structural Properties after 56 Fe +26 Radiation-Induced Changes in Body Mass. Radiat. Res. 170, 201- 207 (2008).

12. Shane A. Lloyd, Eric R. Bandstra, Jeffrey S. Willey, Stephanie E. Riffle, Leidamarie Tirado-Lee, Gregory A. Nelson, Michael J. Pecaut, Ted A. Bateman, Effect of proton irradiation followed by hindlimb unloading on bone in mature mice: A model of long-duration spaceflight, DOI: http://dx.doi.org/10.1016/j.bone.2012.07.001.

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